Professor Nicolas Abatzoglou
Professor, Chemical Engineering,
Sherbrooke (Quebec),
CANADA
E-mail: Nicolas.Abatzoglou@usherbrooke.ca

Co-Authors

Pierre-Philippe Lapointe-Garant
Université de Sherbrooke,
Sherbrooke (Quebec)
Wyeth Inc., St-Laurent (Quebec),
CANADA

Jean-Sébastien Simard
Wyeth Inc., St-Laurent (Quebec),
CANADA

 
Abstract: The Quality by Design (QbD) guideline of the USA Food & Drug Administration (FDA) and of the International Conference on Harmonisation (ICH) became lately the major driver of pharmaceutical processes optimization. The majority of these processes are complex and consequently multivariate. Although new insights have improved the knowledge on the phenomena taking place, it is not usually possible to develop deterministic models. Processes involving powders handling like the multi-component pharmaceutical formulations blending are common and the real-time monitoring of their physico-chemical attributes is challenging.
This QbD initiative is nowadays possible through the use of Process Analytical Technologies (PAT). In this work we propose a multivariate analysis of a V-blender mixing unit operation using an in-line Near-Infra Red (NIR) measurement technique.
For the NIR measurements, a system, consisting of an Axsun IntegraSpec XLP 410 spectrometer connected to an IP-65 encased optical measuring head (sampling probe) through a 1-meter length umbilical wire cord, was used. It uses the Diffuse Reflectance Sampling technology and provides a 40 mm spot size with a spectral range of 1350 nm to 1800 nm. The methodology includes the following steps: (1) modification of a nominal 1 ft³ (30 l) V-blender unit to accommodate Axsun’s NIR spectroscopy system; (2) 3 experimental runs, each with different mixing time, while monitoring powder homogeneity with NIR spectroscopy; (3) acquisition of 10 powder samples after each run from predetermined locations in the V-blender, evaluated both with Axsun NIR spectrometer and current QA/QC Lab methods, to determine mixing end point and (4) data analysis using SIMPA-P+ and GRAMS chemometrics softwares.
Two qualitative algorithms (Analysis of Spectral Variance and Distance Analysis using Hostelling T2) for real-time homogeneity determination are developed and their efficiency is evaluated. A quantitative model was derived and tested with success; it relies on the development of a Partial Least Squares (PLS) model in a principal component hyperspace which better describes the blending information.
In all cases, the size of the acquired information is not comparable to the classical “thief analysis” and the result (prediction of the mixing end point) proved equally or more efficient than with actually employed quality control protocols. In addition, this information can be obtained in real-time using chemometric models. The time savings are huge when compared to classical laboratory analysis (i.e. High Pressure Liquid Chromatography). It is expected that any one of the presented NIR analyses can be beneficial on many aspects of pharmaceutical blending, such as: (1) Real-time quality monitoring of current manufacturing batches; (b) Improve process efficiency and performance by selecting adequate process parameters and blending time; (3) Quality by Design (QbD) initiatives during the development of blending processes for new formulas.

Brief biography of the speaker:
Dr. Nicolas Abatzoglou is full professor at the department of Chemical Engineering of the Universite de Sherbrooke.
He has earned his Ph.D from the NTU Polytechnic School Metsovion, Athens, Greece in 1989. He is co-founder with Professor Chornet of the company Enerkem Technologies Inc., a spin-off of the Universite de Sherbrooke; Enerkem commercializes technologies in the field of energy from renewable resources. N. Abatzoglou has fulfilled the role of vice-president, technology, from 1999 to 2002 to insure the start-up and the necessary technology transfer during the first three years of the company.
He has a career of many years at both the academic and industrial levels. He is a known researcher in the field defined at the junction of Energy & Environment. He represented Canada at the International Energy Agency (Gasification Task) from 1997-2001 and was the secretary of the Board of Directors and the Executive Committee of the AQME from 1996-2000. A specialist of the chemical reactors and the use of granular materials in reactive and non-reactive environments Prof. N. Abatzoglou has focused his research activities during the six last years to:
a) Establish industry-university R&D collaborative programs with pharmaceutical companies (Wyeth and Merck-Frosst) to study the mechanisms of particulate matter segregation and develop new prediction tools in order to improve the Design and operation protocols of industrial processes within a process Analytical technologies (PAT) context.
b) Design, optimize, model and scale-up of a H2S reactive adsorption process for biogas purification in collaboration with an industrial partner (commercialized by Bio-Terre).
c) Study water and dry reforming of methane, ethanol and biofuels for catalyst-supported SOFC application (recent US Patent application).
d) Develop a technology for Carbon sequestration through CO2 (dry) reforming (recent US patent Application).
e) Establish a knowledge base for the study and improvement of technologies leading to higher alcohols and green diesel synthesis from biosyngas (recently approved CRD/NSERC Project).
f) Study and simulate the behavior of a new granular hot gas mobile bed filter, patented lately (USA & Canada).
His production as a researcher includes more than 50 publications in scientific reviews, international conferences, patents and a book chapter. He currently supervises or co-supervises 10 graduate students, a post-doc fellow and 3 undergraduate students in specialty projects or training sessions. He has won twice the first price in environmental R&D at the Quebec Eastern Townships.
He is a recognized chemical engineering teacher (2002, 2003, 2004, 2005, 2006 Bazinet awards for the best Chem. Eng. Professor) at the department of Chem. Engineering of the Universite de Sherbrooke. He teaches mainly: Design of Chemical Processes, Reactor Engineering and Pharmaceutical Process Engineering.
Prof. Abatzoglou is trilingual (French, English, Greek) with an average but functional knowledge of Spanish. He has a wide cultural education and a natural ability in team motivation and hard work.